Gastrectomy induces impaired insulin and glucagon secretion:: evidence for a gastro-insular axis in mice

1. Mice were subjected to gastrectomy (GX) or food deprivation (24 h). The release of insulin and glucagon in response to different secretagogues was monitored in vivo and in isolated islets 3-4 weeks after surgery. 2. GX animals responded to glucose with an impaired glucose tolerance and a poor increase in plasma insulin. Islets from GX or food-deprived mice displayed impaired insulin release to high glucose and enhanced glucagon release at low glucose. 3. After GX the insulinogenic index, Delta insulin (mu U ml(-1))/Delta glucose (mg ml(-1)), was suppressed by 65% after oral glucose and by 59% after I.V. glucose. The integrated insulin response after oral glucose was reduced by 90 % in GX mice. After I.V. glucose the reduction was 67 %. 4. Carbachol-induced insulin release in. vivo was reduced after food deprivation and exaggerated after GX. Carbachol-stimulated glucagon secretion was suppressed after GX and after food deprivation. A similar pattern was found in vitro. 5. Cyclic AMP activation (by the phosphodiesterase inhibitor isobutylmethylxanthine or the adenylate cyclase stimulator forskolin) induced a greater insulin response in EX or food-deprived mice than in sham-operated, fed mice. A similar pattern was found in vitro. The glucagon response was enhanced in, vitro but not in vivo. 6. Crude extracts of rat oxyntic mucosa enhanced basal as well as glucose-induced insulin release from isolated islets, whereas glucagon release was markedly inhibited. The effects were dose dependent, the inhibition of glucagon release being achieved at lower concentrations than the potentiation of glucose-induced insulin release. The active principle was inactivated by incubation with trypsin or leucine aminopeptidase. 7. The data suggest that a circulating agent, probably a peptide, from gastric oxyntic mucosa stimulates glucose-induced insulin secretion. It also suppresses glucagon secretion. The GX evoked impairment of the insulin (and glucagon) response to glucose is partly compensated for by an enhanced insulin response to cholinergic and/or cyclic AMP activation.